This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Oakley, A. E. Articles by Karsch, F. J. PubMed PubMed Citation Articles by Oakley, A. E. Articles by Karsch, F. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL HYDROCORTISONE PROGESTERONE

Role of Estradiol in Cortisol-Induced Reduction of Luteinizing Hormone Pulse Frequency

Department of Molecular and Integrative Physiology and Reproductive Sciences Program (A.E.O., K.M.B., E.R.W., F.J.K.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Physiology (A.J.T.), Monash University, Clayton, Victoria 3800, Australia

Address all correspondence and requests for reprints to: Fred J. Karsch, Department of Molecular and Integrative Physiology, Room 7712B Medical Sciences II, University of Michigan, Ann Arbor, Michigan 48109. E-mail: fjkarsch{at}umich.edu.

Precise control of pulsatile GnRH and LH release is imperative to ovarian cyclicity but is vulnerable to environmental perturbations, like stress. In sheep, a sustained (29 h) increase in plasma cortisol to a level observed during stress profoundly reduces GnRH pulse frequency in ovariectomized ewes treated with ovarian steroids, whereas shorter infusion (6 h) is ineffective in the absence of ovarian hormones. This study first determined whether the ovarian steroid milieu or duration of exposure is the relevant factor in determining whether cortisol reduces LH pulse frequency. Prolonged (29 h) cortisol infusion did not lower LH pulse frequency in ovariectomized ewes deprived of ovarian hormones, but it did so in ovariectomized ewes treated with estradiol and progesterone to create an artificial estrous cycle, implicating ovarian steroids as the critical factor. Importantly, this effect of cortisol was more pronounced after the simulated preovulatory estradiol rise of the artificial follicular phase. The second experiment examined which component of the ovarian steroid milieu enables cortisol to reduce LH pulse frequency in the artificial follicular phase: prior exposure to progesterone in the luteal phase, low early follicular phase estradiol levels, or the preovulatory estradiol rise. Basal estradiol enabled cortisol to decrease LH pulse frequency, but the response was potentiated by the estradiol rise. These findings lead to the conclusion that ovarian steroids, particularly estradiol, enable cortisol to inhibit LH pulse frequency. Moreover, the results provide new insight into the means by which gonadal steroids, and possibly reproductive status, modulate neuroendocrine responses to stress.